title: Synthesis and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[11C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one, a potential PET tracer for growth hormone secretagogue receptor (GHSR).
abstract: The peptide hormone ghrelin mediates through action on its receptor, the growth hormone secretagogue receptor (GHSR), and is known to play an important role in a variety of metabolic functions including appetite stimulation, weight gain, and suppression of insulin secretion. In light of the fact that obesity is one of the major health problems plaguing the modern society, the ghrelin signaling system continues to remain an important and attractive pharmacological target for the treatment of obesity. In vivo imaging of the GHSR could shed light on the mechanism by which ghrelin affects feeding behavior and thus offers a new therapeutic perspective for the development of effective treatments. Recently, a series of piperidine-substituted quinazolinone derivatives was reported to be selective and potent GHSR antagonists with high binding affinities. Described herein is the synthesis, in vitro, and in vivo evaluation of (S)-6-(4-fluorophenoxy)-3-((1-[(11)C]methylpiperidin-3-yl)methyl)-2-o-tolylquinazolin-4(3H)-one ([(11)C]1), a potential PET radioligand for imaging GHSR.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Potter
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Holt
authors.forename: Paige
authors.initials: P
authors.lastname: Finley
authors.forename: Ursula
authors.initials: U
authors.lastname: Scheffel
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
mesh_terms: D000818:Animals; D016466:CHO Cells; D002250:Carbon Radioisotopes / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D054440:Receptors, Ghrelin / Q000032:analysis* / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; D052999:Quinazolinones; D019275:Radiopharmaceuticals; D054440:Receptors, Ghrelin